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drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (CAR T)
drug_description
Autologous CD19-directed CAR T cells (19-28z CAR with CD28 and CD3ΞΆ signaling domains) engineered to secrete IL-12; includes a truncated EGFR (EGFRt) tag for tracking and potential cetuximab-mediated depletion.
nci_thesaurus_concept_id
C204501
nci_thesaurus_preferred_term
EGFRt/19-28z/IL-12 CAR T-lymphocytes
nci_thesaurus_definition
A preparation of T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) fused to the extracellular, transmembrane and intracellular signaling domains of the T-cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (19-28z), a truncated form of the human epidermal growth factor receptor (EGFRt), and the human pro-inflammatory cytokine interleukin-12 (IL-12), with potential immunostimulating and antineoplastic activities. Upon administration, EGFRt/19-28z/IL-12 CAR T-lymphocytes are directed to and induce selective toxicity in CD19-expressing tumor cells. In addition, the administered T-cells secrete IL-12 which induces the secretion of interferon-gamma (IFN-g), promotes the activation of natural killer cells (NKs), and induces cytotoxic T-lymphocyte (CTL) responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The CD28 co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. The inclusion of the CD28 signaling domain may increase proliferation of the T-cells and their antitumor activity compared with the inclusion of the CD3-zeta chain alone. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt facilitates both the in vivo detection of the administered T-cells and the elimination of the administered T-cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells engineered with an anti-CD19 CAR containing CD28 and CD3zeta signaling domains recognize CD19 on B-cell malignancies, become activated, proliferate, and kill targets via cytotoxic effector mechanisms. The cells are further engineered to secrete IL-12, which enhances Th1/IFN-gamma responses, activates NK cells, and augments cytotoxic T-cell activity to strengthen antitumor immunity. A truncated EGFR (EGFRt) tag enables in vivo tracking and optional depletion of the cells via cetuximab-mediated ADCC as a safety switch.
drug_name
EGFRt/19-28z/IL-12 CAR T-lymphocytes
nct_id_drug_ref
NCT06343376